In 20-40% of human breast cancers the erbB-2 or neu gene is amplified leading to mRNA and protein overexpression. This overexpression is likely to be involved in either the initiation or progression of these tumor cells. Amplification of the erbB-2 gene has been linked to a poorer prognosis. In phase I, we propose to generate monoclonal and polyclonal antibodies to extracellular as well as intracellular regions of the erbB- 2 protein. We will prepare antigen from two sources: mouse fibroblasts expressing large amounts of the human erbB-2 protein and bacteria genetically engineered to express specific regions of the erbB-2 protein. The resulting antibody preparations will be tested for their ability to specifically recognize human erbB-2 protein. In phase II, we will explore the uses of these antibodies in diagnosis and therapy of breast cancer.